After ingestion of food or beverages that contain carbohydrates, these carbohydrates are broken down during digestion and thereby converted to mono- and disaccharides, mostly glucose. Glucose is a source of energy for the cells of the organism. This energy is yielded within the cells through glycolisis and subsequent reactions of the citric acid cycle. Glucose is transported to the cells via the organism's blood stream. Therefore, ingestion of food will have an influence on the concentration of glucose within the blood stream; i.e. the blood glucose level will change.
There is significant evidence that a calorie-restricted diet promotes good health (U.S. National Institute on Aging, Primate Aging Study). Humans are recommended to receive between 45-65% of daily caloric intake from carbohydrates. Therefore, one benefit of a calorie-restricted diet is an overall reduction of blood glucose levels. High blood glucose concentrations have been correlated with numerous health problems including oxidative stress, micro- and macro-vascular tissue damage, heart disease, hypertension and Type II diabetes.
Certain carbohydrate-containing foods are rapidly absorbed into the blood stream, causing a rapid increase of blood glucose levels and acutely over-supplying the body with energy. Such carbohydrates, as refined flour or pure glucose, require very little digestion to release their sugars and are therefore rapidly absorbed into the blood, often at a rate which exceeds the body tissue's ability to metabolize the excess energy. Carbohydrates which are more difficult to digest or to absorb appear in the blood stream at a slower pace following ingestion; and are therefore less likely to cause a significant rise in blood glucose levels. However, any meal that contains a large quantity of carbohydrates will eventually result in elevated blood glucose, as the body's rate of metabolism lags behind the inevitable release of sugars from food in the gut. The hyperglycemic effect of excess carbohydrate consumption is more pronounced in individuals who suffer from insulin resistance and/or impaired glucagon supression, conditions that characterize Metabolic Syndrome and Type II diabetes. Even in healthy individuals, meals that contain large quantities of rapidly absorbed carbohydrates can result in a fast rise of blood glucose followed by a rapid decline (evidence of higher circulating insulin concentrations in response to the glucose spike).
The medical significance of the magnitude of blood glucose fluctuations is a controversial topic that has been the subject of extensive research (see e.g. G. Bolli, “Glucose Variability and Complications.”, Diabetes Care, Vol. 29, No. 7, July 2006 (Editorial); M. Brownlee, “Glycemic Variability: A Hemoglobin A1c-Independent Risk Factor for Diabetic Complications.” (Reprinted) JAMA, Apr. 12, 2006—Vol 295, No. 14. pp. 1707-1708; K. Close, Diabetes Close Up, December 2005, No. 54, DCU on Glycemic Variability; B. Hirsch et al., “Should minimal blood glucose variability become the gold standard of glycemic control?” Journal of Diabetes and Its Complications.”, Vol. 19 (2005) pp. 178-181; I. Hirsch, “Is A1c the Best Measure of Glycemic Control?” Business Briefing, North American Pharmacotherapy. 2005; I. Hirsch, “Glycemic Variability: It's Not Just About A1C Anymore!” Diabetes Technology & Therapuetics, Vol. 7, No. 5, 2005; L. Monnier et al., “Activation of Oxidative Stress by Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglycemia in Patients With Type 2 Diabetes.”, JAMA 2006; 295:1681-1687; J. Murphy, “RISK FACTORS: Acute Glycemic Variability Correlates With Oxidative Stress.” 2005 DiaVed, Inc. May 2006).
Potential consequences of chronic high glycemic fluctuations cited in the literature include an increased risk of Type II diabetes, hypertension and heart disease. A causal link between the magnitude of glycemic fluctuations and the risk of chronic disease is supported by clinical evidence of increased free radical production at the cellular level, resulting in vascular tissue damage. High levels of glycemic fluctuation have also been associated with hyperinsulinemia, mood swings, appetite stimulation, fatigue and compromised athletic performance. Severe fluctuations in blood sugar have further been correlated with hunger pangs (see e.g. U.S. Pat. No. 6,905,702, Los Angeles Children's Hospital) and chronic health problems; frequent fluctuations with high amplitude have been correlated with oxidative stress, micro- and macro-vascular tissue damage.
Therefore, a meal will preferably release carbohydrates into the blood slowly, producing a gradual rise that is manageable by the body's tissues. For these reasons, also to promote appetite control and safety for people trying to lose weight, nutritionists Jenny Brand-Miller and Thomas Wolever recommend a diet that minimizes the magnitude of glycemic response.
There are different ways of quantifying the progression of a glucose level in an individual. One aspect of the change of the concentration of glucose relates to the rate at which the ingested food or beverage is able to increase the blood glucose level and the length of time the blood glucose remains elevated. This is usually denoted by the term “glycemic response”.
There are established metrics to evaluate the glycemic impact of carbohydrate-containing foods, namely the Glycemic Index (GI) and the Glycemic Load (GL). The Glycemic Index (GI) is proportional to the area under the curve (AUC) when blood glucose concentration is plotted against time, wherein only the two hours following the ingestion of a fixed portion of carbohydrate (usually 50 g) are considered. The AUC of the test food is divided by the AUC of a reference food portion (either glucose or white bread) of equal carbohydrate content and multiplied by 100. The average GI value is calculated from data collected in a sample population and is available in GI tables (e.g. J. Brand-Miller, K. Foster-Powell, “Shopper's Guide to GI Values”, Marlowe & Company, 2007). Glycemic Load (GL) takes into account the portion size of the ingested food. It is calculated as the quantity (in grams) of its carbohydrate content, multiplied by its GI, and divided by 100.
In summary, glycemic response relates to the quantitative aspects of the development of the glucose level, i.e. to the rate at which the ingested food or beverage is able to increase the blood glucose level and the length of time the blood glucose remains elevated. The usual measures are based on AUC which primarily quantifies the amount of carbohydrates consumed.
However, two progressions of the glucose level in a subject may have a completely different shape but still correspond to the same AUC value. Therefore, AUC cannot provide the full picture. Besides the merely quantitative aspects described above there are further aspects of a more qualitative nature, relating to the “quality” of the glucose response, generally to how much a person's blood sugar fluctuates over time, and therefore to the quality of carbohydrates consumed. For example, pure refined sugar is known to cause a spike in blood glucose followed by a rapid decline. It is therefore reasonable to assume that a measured spike and decline in blood glucose is indicative of food consumption in which the food contained a high portion of fast-acting carbohydrates.
From the field of diabetes care methods are known for quantifying the degree of fluctuation in a glucose concentration in the bloodstream or interstitial fluid over time, especially during the time following a meal or another glucose-altering event such as physical activity or hormone level changes. For the purposes of this document, these methods and the quantitative measures they provide are denoted by the general term Glycemic Variability (GV). GV characterizes the fluctuations (frequency and magnitude) of the glucose concentration.
For the purpose of assessing GV, the glucose response may be monitored by spot blood glucose measurements (SMBG), such as e.g. one month of routine self-monitoring data, or by continuous glucose monitoring (CGM) with much higher measurement frequencies, see e.g. the following articles by B. Kovatchev et al.: “Methods for Quantifying Self-Monitoring Blood Glucose Profiles Exemplified by an Examination of Blood Glucose Patterns in Patients with Type 1 and Type 2 Diabetes.”, Diabetes Technology & Therapuetics, Vol. 4, No. 3, 2002; “Algorithmic Evaluation of Metabolic Control and Risk of Severe. Hypoglycemia in Type 1 and Type 2 Diabetes Using Self. Monitoring Blood Glucose Data.”, Diabetes Technology & Therapuetics, Vol. 5, No. 5, 2003; “Quantifying Temporal Glucose Variability in Diabetes via Continuous Glucose Monitoring; Mathematical Methods and Clinical Application.”, Diabetes Technology & Therapuetics, Vol. 7, No. 6, 2005; “Evaluation of a New Measure of Blood Glucose Variability in Diabetes.”, Diabetes Care, Vol. 29, No. 11, November 2006. pp. 2433-2438.
There are numerous published metrics to quantify different aspects of glycemic variability, both during a single day (e.g. CONGA, see C M McDonnell et al. “A Novel Approach to Continuous Glucose Analysis Utilizing Glycemic Variation.”, Diabetes Technology & Therapuetics, Vol. 7, No. 2, 2005) and also over longer periods of time (i.e. LBGI/HBGI, see B. Kovatchev et al., “Algorithmic Evaluation of Metabolic Control and Risk of Severe Hypoglycaemia in Type 1 and Type 2 Diabetes Using Self-Monitoring Blood Glucose Data,” Diabetes Technology and Therapeutics, Volume 5, Number 5, 2003. pp. 817-828).
To date, there is no method of GV that is accepted in the clinical practice of diabetes care, although there exists growing interest in the medical relevance (and controversy, see Kilpatrick et al. 2006). GV can be used to describe general trends over long periods of time, compatible with the long time monitoring of HBA1c; or to focus on events of short duration, such as meals or overnight. The results of a determination of glycemic variability may be used to predict health risks for the patient, such as the patient's risk of hypoglycemia, including intra-day risk, intra-week risk or a general risk of hypoglycemia. Furthermore, GV may be correlated with the other health risks described above, such as oxidative stress and macro- or micro vascular tissue damage. Similarly, GV may also provide a way to stage Type II diabetes, i.e., “less stability indicates less metabolic control.”
In summary, today GV is considered to be a way of assessing the quality of diabetes control. However, clinicians do not agree on what “good” control is. Because of this, it is difficult to define a universal metric. The only references available are the measurements performed on healthy patients. A therapy is “good” if it leads to glucose excursions similar to the ones observed in healthy patients.
However, despite the fact that the blood sugar fluctuations do not only affect the health of diabetic people but also of the health of individuals who do not suffer uncontrolled metabolic disorders and do not require exogenous insulin, the potential of GV has not yet been fully exploited outside the field of diabetes care. Whereas the quantity of the carbohydrates consumed can be partly taken into account by using GI or GL tables, the glycemic variability is not systematically observed. Despite the wealth of literature available on metabolism and nutrition, the actual physiological effect of actual ingested meals (both food composition and quantity) remains a largely speculative “guessing game,” leading to widespread confusion, denial and frustration among dieters. This is also true for the use of GL tables which bases on the assumption that all labeled food items are assumed to have the same effect on the blood glucose level of any consumer. As stated by Connie Gutterson in her article “Syndrome X: Prescribing the Right Carbohydrates”, “it is the quality of the foods consumed that will impact long term health. It is our professional responsibility to address this but to also provide the link between science and food.”